Nuclear medicine, which uses radioactive chemical elements called radionuclides to diagnose or treat diseases, has grown tremendously over the past 50 years. Nuclear medicine encompasses a variety of imaging devices and therapeutics that use radionuclides. Nuclear imaging devices, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) scans, work by tracking radioactive chemicals that are swallowed, inhaled, or injected into the body, where they accumulate in the organ or tissue of interest and reveal biochemical changes. Such imaging devices enable physicians to diagnose diseases including cancer, cardiovascular disease, and neurological disorders (e.g., Alzheimer's and Parkinson's diseases) in their initial stages. These techniques allow doctors to obtain medical information that would otherwise require more costly and invasive procedures like surgery or biopsy. Nuclear imaging devices are also valuable for conducting research on the biology of human diseases and for developing and testing new treatment approaches.
Although nuclear medicine has already made enormous contributions to biomedical research and disease management, its promise is only beginning to be realized in such areas as drug development, preventive health care, and personalized medicine. However, there remain two major problems in the field of nuclear medicine and imaging: 1) the complex and expensive chemistry infrastructure required for traditional radiolabeling or radionuclide production, and 2) the difficulty in producing high affinity targeted-(radio) ligands specific for particular disease.
Quantitative imaging of liver fibrosis or fibrogenesis has been elusive. Integrin αvβ6 mediates attachment of activated epithelia to fibronectin, vitronectin, and tenascin {Breuss, 1995; Midwood, 2006} and activates profibrogenic cytokine TGFβ {Munger, 1999} implying its instrumental role in driving fibrogenesis. Integrin receptors frequently recognize a core amino acid sequence, Arg-Gly-Asp (RGD), in their target ligands. Therefore, inhibitors with the RGD sequence can inhibit one or a small subset of such RGD-dependent integrins, and are invaluable in defining their biological functions. However, peptidic inhibitors have several disadvantages as low molecular weight inhibitors, including their instability to serum degradation (which can be circumvented by use of small cyclic peptides {Kessler, 1982}, and poor pharmacokinetics. Nevertheless, non-RGD peptides have been discovered with high specificity and inhibitory activity for αvβ6 {Kloczewiak, 1984; Kraft, 1999}, and, as of yet, non-peptidic inhibitor of αvβ6 are not known for use in nuclear imaging of αvβ6 in liver fibrosis.